DETECTION OF AUTOANTIBODIES TO RECOMBINANT MITOCHONDRIAL PROTEINS IN PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS
DETECTION OF AUTOANTIBODIES TO RECOMBINANT MITOCHONDRIAL PROTEINS IN PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS
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DOI：
10.1056/nejm198905253202104
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发表时间：
1989-05-25
影响因子：
158.5
通讯作者：
GERSHWIN, ME
中科院分区：
文献类型：
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作者：
VANDEWATER, J;COOPER, A;GERSHWIN, ME
原发性胆汁性肝硬化的特征在于存在对74和52千道尔顿（kd）的蛋白质具有特异性反应性的线粒体自身抗体。74 kd线粒体蛋白是丙酮酸脱氢酶复合物的E2组分-二氢硫辛酰胺乙酰转移酶，52 kd蛋白是支链α-酮酸脱氢酶复合物的等效E2组分-二氢硫辛酰胺酰基转移酶。目前检测这些蛋白抗体的方法缺乏特异性或敏感性，或者耗时且不易获得，因此我们开发了一种酶联免疫测定法来定量原发性胆汁性肝硬化患者的特异性抗线粒体抗体。重组多肽编码的74-kd和52-kd线粒体自身抗原被用来分析217编码的血清样本，其中包括93例原发性胆汁性肝硬化患者和124名对照，我们的免疫分析，免疫印迹和免疫荧光检测的反应性。93例原发性胆汁性肝硬化患者中89例的血清样本与丙酮酸脱氢酶-E2或支链α-酮酸脱氢酶蛋白反应。没有124个对照样本从健康志愿者（n = 86）或原发性硬化性胆管炎（n = 38）有显着reaction.Our结果表明，使用重组，克隆自身抗原提供了一个简单，准确，快速的方法定量和监测特异性线粒体自身抗体的水平在原发性胆汁性肝硬化患者的血清中。（N Engl J Med 1989; 320：1377-80.）
Primary biliary cirrhosis is characterized by the presence of autoantibodies to mitochondria with specific reactivity to proteins of 74 and 52 kilodaltons (kd). The 74-kd mitochondrial protein is the E2 component — dihydrolipoamide acetyltransferase — of the pyruvate dehydrogenase complex, and the 52-kd protein is the equivalent E2 component — dihydrolipoamide acyltransferase — of the branched-chain α-keto acid dehydrogenase complex. Current methods for the detection of antibodies to these proteins lack specificity or sensitivity, or they are time-consuming and not readily available.We therefore developed an enzyme-linked immunoassay to quantify specific antimitochondrial antibodies in patients with primary biliary cirrhosis. Recombinant polypeptides coding for both the 74-kd and the 52-kd mitochondrial autoantigens were used to analyze 217 coded serum samples, including samples from 93 patients with primary biliary cirrhosis and 124 controls, for reactivity by our immunoassay, immunoblotting, and immunofluorescence testing. Serum samples from 89 of the 93 patients with primary biliary cirrhosis reacted with either the pyruvate dehydrogenase-E2 or the branched-chain α-keto acid dehydrogenase protein. None of the 124 control samples from healthy volunteers (n = 86) or patients with primary sclerosing cholangitis (n = 38) had significant reactivity.Our results indicate that the use of recombinant, cloned autoantigens provides a simple, accurate, and rapid method of quantifying and monitoring the levels of specific mitochondrial autoantibodies in the serum of patients with primary biliary cirrhosis. (N Engl J Med 1989; 320: 1377–80.)